Discussions on the synthesis of LSD

Taken from the Hive & Usenet
Plus some reference Lists at the end

HTML by Rhodium

Kaff (posted 05-16-98)

It just occurred to me that noone ever mentions acid. I
have Fester's book Practical LSD Manufacture but that's
about as practical as buying a wheat farm just to make
acid. Yeah right Hawaiin Baby woodrose seeds and morning
glory seeds have some lysergic acid, but why aren't there
any new methods?

drone 342 (posted 05-16-98)

I agree, Fester's LSD book was a major disappointment --
yet one more reason to loath the guy. There is an
advancement, one which Fester didn't include, which is
the use of POCl3 as a dehydrating reagent in the
condensation of lysergic acid with diethylamine. Check
out Rhodium's page, as well as hyperreal for more info on
this new developement.

The wierdest part about it is that it was developed by
our friends over at the Edgewood Arsenal in Maryland
during the mid-seventies -- the good people who lead the
world in cutting-edge chemical warfare technology and
supply the intelligence community with all the wierd shit
they use. These are the same folks who stockpiled QNB in
multi-kilo quantities right into the eighties, as well as
the freaky things they don't tell anyone about. Some day,
I want a tour of that place.

Anyways, the important thing to keep in mind, which
really shows yet again how much Fester talks out of his
ass, is that all the seeds, fungi, and other biomass is
NOT the way to allocate your lysergic compounds for this
reaction. Anybody who makes it on a big scale is using
most liekely ergot alkaloids from a commercial source --
foreign pharmacy companies, etc. Its not that hard to get
your hands on an ounce or two of ergotamine or ergonovine
if you put your noggin to it. Hell, even bromocryptine
will work (remove the bromine by maing the grignard out
of it, then hydrolyzing it. As long as its done gently,
no funky additions, olgermizations or whatever, will
happen.)

I've been waiting for someone to bring this subject up.
Ask and you shall recieve.

KrZ (posted 05-17-98)

Whats wrong with Hawaiin Baby Woodrose? When your making
something where 1 dose=50 micrograms a pound of HWBR goes
a long ways... Does fester talk about culturing as a
source in an incubator?

Fan of Shulgin (posted 05-17-98)

IMHO culturing the ergot fungus in the best method by far
for producing LSD. Even someone with absolutely no
knowledge of microbiology can culture ergot. And as to
obtaining the fungus, it can be found in most large
fields of rye. This is no joke, wait just until harvest
time and go out and have a look for the 'heads'. The
beauty of growing the Claviceps is that you can keep it
alive for ever if you are careful, and thus have an
almost never ending supply of raw material.

It is worth noting, that this is the method that most
illegal acid labs operate (look up operation Julie in the
UK!). Even producing acid on a small scale requires you
to prepare shit loads of the precursors, because even
working under red light at low temperatures and low
humidity does not have that great an effect on keeping
yields high (a 20% yield in LSD manufacture is considered
a great success). Remember LSD is inherantly unstable!

Anyway - LSD synthesis, Claviceps cultivation etc are one
of the most talked about drug manufacturing methods on
the net. Have a good long search around!

drone 342 (posted 05-17-98)

I'm telling you guys, mushroom cultivation IS NOT where
its at! As far as I can tell, this is not as common of a
procedure as people believe. Why? Ever look at the amount
of solvents entailed in extracting the stuff? This is a
way too involved process that uses far too many
resources. MAYBE there's some lab that does this, but
it's just not practical. Besides, this bioproduction
entails the chemist mastering a whole bunch more skills
than the tricky ones already required.

I stand by my procedure as THE ONE TRUE WAY(tm), or at
least the best of the one true ways. Think about it:
Bromocryptine into bromolysergic acid. Bromolysergic acid
into bromolysergic acid diethylamide. Bromolsyergic acid
diethylamide into its respective grignard reagent.
Grignard reagent decomposition into LSD. Add a dash of
tartaric acid, and chromatograph it. All pretty simple
procedures -- relatively speaking.

Bromocryptine is easy to get in reasonable quantities.
Other ergot alkaloids are also available, and would alow
the chemist to skip a debromination step or two as well.

While some believe that LSD is only worthwhile on a
mega-huge scale of ounces at a time, I contend that using
the sources I suggest, that a gram-size batch would still
be a very attractive endevor.

HBWR seeds might be a decent way to go, I agree, but I
prefer pill extracting any day. Considering also the
price and notriousness of this as a source, other sources
should be investigated more thotoughly. How much does a
kilo of seeds go for nowadays?

Still, here's another source. Grain companies have a lot
of fancy-shmancy equiptment I've been told, soley to
remove claviceps from our food supply. This means that
every harvest season, your local grain elevator has got
pounds of ergot-ladden grain that they normally throw
away. This I heard from a friend of mine who worked in a
grain elevator -- lost contact with him since my chemical
skills were upgraded. This is worth some investigating.

Anyways, I agree that far too little research is being
done into these matters, and I'd like to see more
discussion of the chemistry of Hoffmann's baby. The
chemistry IS above kitchen production conditions, but not
out of reach for the semi-elite of The Hive's Chemical
Guard. By eliminating the riduculous, over-complicated
bullshit procedures out there, and replacing them with
simpler, more practical means, the small circle of people
willing-and-able to perform this most sacred of chemistry
is widended considerably.

KrZ (posted 05-18-98)

Drone, c'mon, we are not talking about mushrooms here, wake up son... Mushrooms growing right on top of rye
plants, that would look prety silly.. All you need is a sample, some .2% agar plates and some sterile technique,
not exactly skill-requiring stuff..

drone 342 (posted 05-18-98)

KrZ said: Drone, c'mon, we are not talking about mushrooms here, wake up
son... Mushrooms growing right on top of rye plants, that would look prety silly. All you need is a sample,
some .2% agar plates and some sterile technique, not exactly skill-requiring stuff.

KrZ:

Sorry, I suffer from a mild case of irony deficiency, and so its hard for me to tell when folks are pulling my leg.
I wholeheartedly aprove of and endorse mushroom cultivation -- provided it is of my favorite basidiomycetes genus that starts with the letter "p".

However, I think you'll discover claviceps is harder than you think. Ever try to get a pure culture of that stuff?
If you go through any of the research collections or biotech companies, you're going to have to fill out more
paperwork than you'd believe -- not because its laden with ergot goodness, but because its considered a
agriculturally harmful organism. It's about as involved as filling out forms for the purchasing of an
encapsulating machine. If you choose to isolate your own strain from the field, good luck. You got a 2-month or so
window of time to collect it, and then comes the isolation process. Then once you have pure claviceps,
you're going to have to isolate a decent-producing heterokaryote from your collection, which you may or may
not have. Once you manage THAT, then comes the petri dish phase, followed by the initial submerged culture for
producing seed stock, then finally the large-scale submerged culture to yield a a sludge of filaments you
gotta strain out, dry, then extract.

Yuck. There are a lot of professional folks out there who's entire days, nay, entire careers relovle around
ergot production. I rather rely on the fruits of their labor and save all the schmassle that this project would otherwise entail.

Think about it. I honestly feel the main detractor from more people producing LSD is this ergot culturing myth.
Yeah, everyone says "Boy, I sure wish I could make some good acid. All I gotta do is get a chemistry degree under
my belt, get a good lab space, and on top of that, raise a culture of some fucked-up saprophytic fungus that'll
give me gangrene in the process." This is obviously daunting. If you disagree and say its not too much of a
bother, then why aren't more people kicking out kilos of "L"? What I'm proposing is that this fungus cultivation
idea is more of a detriment to acid production than an advantage. Just extract the shit from pills, or go to the
third world where the stuff is cheap, and you can buy it in its straight uncut powder form for pharmaceutical
outlets (there are several countries where you can do this when you know a good pharmacist and have the cake to
do some bribing; believe me, I've looked.)

As simple as ergot cultivation sounds, there's plenty of reasons its not done commonly.

drone 342 (posted 05-18-98)

Oh yeah, and I almost forgot. With bromocriptine, you can do that grignard degredation process as your first couple
steps; this wil cut down on the amounts of POCl3 and Et2N required in the amidation and save you precious
resources. Grignards don't readily add to amides, so you can take advantage of that.

drone 342 (posted 05-20-98)

Okay, so of available precursors for acid, we got:

HBWR

Ipomoea sp.

Claviceps sp.

Ergot alkaloid pills (ergotamine, ergonovine, etc.)

bromocriptine

a few other misc. plants

Seems to me the chemistry and methodology is pretty cut-and-dry -- the main problem is precursor aquisition.
So what other exciting sources might be out there for the ergoloid ring?

drone 342 (posted 05-20-98)

Commodium (posted 05-20-98)

Yeah, looks like (according to that Journal of the AOAC
article) Hawaiian Baby Wood Rose is 0.04 to 0.30 % LSA,
by weight.

drone 342 (posted 05-20-98)

Incidentally, I looked into the possible utilization of
sleepy grass, butit looked like it was full of all sorts
of other alkaloid garbage aside from lisergic acid and
its amides. Chanoclavines, Pyridines, etc. This might be
a good source if anybody knows a good way of separating
the wheat from the chaff in this case. What else besides
HPLC will do the trick? (I have an HPLC machine for my
amusement, but I can only do tiny volumes; besides, half
the point of this research is figuring out ways of doing
this kind of stuff successfully garage-style rather than
just in the lab.)

Also, does anybody else harbor the same loathing for
Fester and his piece-o-shit-excuse-for-an-acid-book as I
do? I mean, he completely missed the POCl3 method, and
left "method X" a mystery (even though its probobly just
as full of shit as the rest of the book.) In addition, he
mistakenly thought propionic anhydride had something to
do with acid chemistry, and then didn't even give a
particularily meaningful synthesis for it. All his
methods looked like rehashes of patents from the earlier
part of this century (available in half a dozen other
publications already,) and the only lysergic acid source
he offers is buying a goddam wheat farm and raising a
crop of moldy rye grain! Even his claviceps raising would
take over a year to accomplish!

So, his book only would be practical for a farmer with a
couple years on his hands, a few 55-gallon barrels of
tech-grade solvents, a lab full of large-scale equiptment
for advanced organic chemical procedures, and some rather
extensive training in organic chemistry. If a person had
all those resources available to them at the same time,
they'd be an idiot if they couldn't find a better way of
going about things than that.

buzzz (posted 05-20-98)

I haven't looked over it a great deal but, the book
Psychedelic Chemistry by Michael Valentine Smith gives
detailed info on lysergic acid and extractions for ergot
extraction from HBWS and states that the seeds yield 7mg
alkaloids/100 g of seeds and that thru the usual steps to
reach the end point of lsd that you get roughly 1g LSD /
kg of seed. the book can be ordered from Loompanics.

drone 342 (posted 05-20-98)

Got a copy of that one already; what library would be
complete without MVS's book? Nothing too
earth-shattering, but still I like it; there's an aura of
honesty to it that you don't see in many other
underground drug books. MVS is sure no formally-trained
chemist, but at least he knew how to operate a copying
machine and give credit where it was due.

Your numbers don't add up.
(7mg ergot/100g HBWR)×(1000g/1kg) does not equal even 1g of
ergot, but I get the general gist of it. I'll give it a
look-see. Thanks for the tip. Considering that a kilo can
be boughten for around $300-$400 dollars, it looks like
it would almost be a good investment (I prefer the
chemistry of drugs where the profit margin is closer to
95-99% rather a mere 75-80%, but hey, its acid.)

KrZ (posted 05-21-98)

LSD has been manufactured illegally since the 1960's. A
limited number of chemists, probably less than a dozen,
are believed to be manufacturing nearly all of the LSD
available in the United States. Some of these manufacturers
probably have been operating since the 1960's.

LSD manufacturers and traffickers can be separated into
two groups. The first, located in northern California, is
composed of chemists (commonly referred to as 'cooks') and
traffickers who work together in close association; typically,
they are major producers capable of distributing LSD
nationwide. The second group is made up of independent
producers who, operating on a comparatively limited scale,
can be found throughout the country. As a group, independent
producers pose much less of a threat than the northern
California group inasmuch as their production is intended
for local consumption only.

Drug law enforcement officials have surmised that LSD
chemists and top echelon traffickers form an insider's
fraternity of sorts. They successfully have remained at
large because there are so few of them. Their exclusivity
is not surprising given that LSD synthesis is a difficult
process to master. Although cooks need not be formally
trained chemists, they must adhere to precise and complex
production procedures. In instances where the cook is not
a chemist, the production recipe most likely was passed on
by personal instruction from a formally trained chemist.
Further supporting the premise that most LSD manufacture is
the work of a small fraternity of chemists, virtually all
the LSD seized during the 1980's was of consistently high
purity and sold in relatively uniform dosages of 20 to 80
micrograms.

LSD commonly is produced from lysergic acid, which is
made from ergotamine tartrate, a substance derived from
an ergot fungus on rye, or from lysergic acid amide, a
chemical found in morning glory seeds. Although
theoretically possible, manufacture of LSD from morning glory
seeds is not economically feasible and these seeds never
have been found to be a successful starting material for
LSD production. Lysergic acid and lysergic acid amide are
both classified in Schedule III of the Controlled Substances
Act. Ergotamine tartrate is regulated under the Chemical
Diversion and Trafficking Act.

Ergotamine tartrate is not readily available in the
United States, and its purchase by other than established
pharmaceutical firms is suspect. Therefore, ergotamine
tartrate used in clandestine LSD laboratories is believed
to be acquired from sources located abroad, most likely
Europe, Mexico, Costa Rica, and Africa. The difficulty
in acquiring ergotamine tartrate may limit the number of
independent LSD manufacturers. By contrast, illicit
manufacture of methamphetamine and phencyclidine is
comparatively more prevelant in the United States because,
in part, precursor chemicals can be procured easily.

Only a small amount of ergotamine tartrate is required to
produce LSD in large batches. For example, 25 kilograms
of ergotamine tartrate can produce 5 or 6 kilograms of pure
LSD crystal that, under ideal circumstances, could be
processed into 100 million dosage units, more than enough to
meet what is believed to be the entire annual U.S. demand
for the hallucinogen. LSD manufacturers need only import a
small quantity of the substance and, thus, enjoy the advantages
of ease of concealment and transport not available to
traffickers of other illegal drugs, primarily marijuana
and cocaine.

Cooking LSD is time consuming; it takes from 2 to 3 days
to produce 1 to 4 ounces of crystal. Consequently, it is
believed that LSD usually is not produced in large
quantities, but rather in a series of small batches.
Production of LSD in small batches also minimizes the loss of
precursor chemicals should they become contaminated during
the synthesis process.

LSD crystal produced clandestinely can be as much as 95-100-percent pure. At this purity - and assuming optimum
conditions during dilution and application to paper - 1 gram
of crystal could produce 20,000 dosage units of LSD.
However, analysis of LSD crystal seized in California over
the past 3 years revealed an average purity of only 62
percent. Moreover, LSD degrades quickly when exposed to
heat, light, and air and is most susceptible to degradation
during the application process and once it is in paper form.
As a result, under less than optimal, real-life conditions,
actual yields are significantly below the theoretically
possible yield: 1 gram of LSD crystal genarally yields
10,000 dosage units of LSD, or approximately 10 million
dosage units per kilogram.

Over the past 30 years, the traditional dilution factor
for manufacturing LSD has been 10,000 doses per 1 gram of
crystal. Therefore, dosage units yielded from high-purity
(95-100-percent pure) LSD crystal would contain 100
micrograms. However, dosages currently seen contain closer
to 50 micrograms. This discrepancy stems in part from
production impurities: during the sythesis process,
manufacturers generally fail to perform a final 'clean-up'
step to remove by-products, thereby lowering the crystal's
purity. Further, though average purity of tested LSD crystal
samples is, as noted, 62 percent, the average potency of
doses analyzed is approximately 50 micrograms rather than 62
micrograms, as would be expected. The diminished potency
can be attributed to distributors who, when applying the
crystal to paper, often 'cheat' by diluting 1 gram of
crystal to produce up to 15,000 or more dosage units.

Pure, high-potency LSD is a clear or white, odorless
crystalline material that is soluble in water. It is
mixed with binding agents, such as spray-dried skim milk,
for producing tablets or is dissolved and diluted in a
solvent for application onto paper or other materials.
Variations in the manufacturing process or the presence of
precursors or by-products can cause LSD to range in color
from clear or white, in its purest form, to tan or even
black, indicating poor quality or degradation. To mask
product difficiencies, distributors often apply LSD to
off-white, tan, or yellow paper to disguise discoloration.

At the highest levels of the traffic, where LSD crystal
is purchased in gram or multigram quantities from wholesale
sources of supply, it rarely is diluted with adulterants, a
common practice with cocaine, heroin, and other illicit
drugs. However, to prepare the crystal for production in
retail dosage units, it must be diluted with binding agents
or dissolved and diluted in liquids. The dilution of LSD
crystal typically follows a standard, predetermined recipe
to ensure uniformity of the final product. Excessive dilution
yields less potent dosage units that soon become unmarketable.

LSD crystal usually is converted into tablet form ('microdots'
that are 3/32 inch or smaller in diameter), thin squares of
gelatin ('window panes'), or applied to sheets of prepared
paper (blotter paper-initially used as a medium-has been
replaced by a variety of paper types). LSD most frequently
is encountered in paper form, still commonly referred to as
blotter paper or blotter acid. It consists of sheets of paper
soaked in or otherwise impregnated with LSD. Often these
sheets are covered with colorful designs or artwork and
are usually perforated into one-quarter inch square,
individual dosage units.

Make up a culture medium by combining the following ingredients in about 500 milliliters of distilled water in a 2 liter, small-neck flask:

Add water to make up one liter, adjust pH 4 with ammonia solution and citric acid. Sterile by autoclaving.

Inoculate the sterilized medium with Claviceps purpurea
under sterile conditions, stopper with sterilized cotton
and incubate for two weeks periodically testing and
maintaining pH 4. After two weeks a surface culture will
be seen on the medium. Large-scale production of the fungus
can now begin.

Obtain several ordinary 1 gallon jugs. Place a two-hole
stopper in the necks of the jugs. Fit a short (6 inch)
glass tube in one hole, leaving 2 inches above the stopper.
Fit a short rubber tube to this. Fill a small (500
milliliter) Erlenmeyer flask with a dilute solution of
sodium hypochlorite, and extend a glass tube from the rubber
tube so the end is immersed in the hypochlorite. Fit a long,
glass tube in the other stopper hole. It must reach near
the bottom of the jug and have about two inches showing
above the stopper. Attach a rubber tube to the glass tube as
short or as long as desired, and fit a short glass tube to
the end of the rubber tube. Fill a large, glass tube (1 inch
x 6 inches) with sterile cotton and fit 1-hole stoppers in
the ends. Fit the small, glass tube in end of the rubber
tube into 1 stopper of the large tube. Fit another small
glass tube in the other stopper. A rubber tube is connected
to this and attached to a small air pump obtained from a
tropical fish supply store. You now have a set-up for pumping
air from the pump, through the cotton filter, down the long
glass tube in the jug, through the solution to the air
space in the top of the jug, through the short glass tube,
down to the bottom of the Erlenmeyer flask and up through
the sodium hypochlorite solution into the atmosphere. With
this aeration equipment you can assure a supply of clean air
to the Claviceps purpurea fungus while maintaining a sterile
atmosphere inside the solution.

Dismantle the aerators. Place all the glass tubes, rubber
tubes, stoppers and cotton in a paper bag, seal tight with
wire staples and sterilize in an autoclave.

Fill the 1-gallon jugs 2/3 to 3/4 full with the culture
medium and autoclave.

While these things are being sterilized, homogenize in a
blender the culture already obtained and use it to inoculate
the media in the gallon jugs. The blender must be sterile.
Everything must be sterile.

Assemble the aerators. Start the pumps. A slow bubbling
in each jug will provide enough oxygen to the cultures. A
single pump can, of course, be connected to several filters.

Let everything sit a room temperature (25°C) in a fairly
dark place (never expose ergot alkaloids to bright light -
they decompose) for a period of ten days.

After ten days adjust the culture to 1% ethanol using 95%
ethanol under sterile conditions. Maintain growth for another
two weeks.

After total of 24 days growth period the culture should
be considered mature. Make the culture acidic with tartaric
acid and homogenize in a blender for one hour.

Adjust to pH 9 with ammonium hydroxide and extract with
benzene or chloroform/iso-butanol mixture.

Extract again with alcoholic tartaric acid and evaporate
in a vacuum to dryness. The dry material in the salt (i.e.,
the tartaric acid salt, the tartrate) of the ergot alkaloids,
and is stored in this form because the free basic material is
too unstable and decomposes readily in the presence of light,
heat, moisture and air.

To recover the free base for extraction of the amide of
synthesis to LSD, make the tartrate basic with ammonia to pH
9, extract with chloroform and evaporate in vacuo.

If no source of pure Claviceps purpurea fungus can be
found, it may be necessary to make a field trip to obtain
the ergot growths from rye or other cereal grasses. Rye
grass is by far the best choice. The ergot will appear as a
blackish growth on the tops of the rye where the seeds are
and are referred to as "heads of ergot." From these heads
of ergot sprout the Claviceps purpurea fungi. They have
long steams with bulbous heads when seen under a strong
glass or microscope. It is these that must be removed
from the ergot, free from contamination, and used to
inoculate the culture media. The need for absolute sterility
cannot be overstressed. Consult any elementary text on
bacteriology for the correct equipment and procedures.
Avoid prolonged contact with ergot compounds, as they are
poisonous and can be fatal.

The whole part with the pump is unecessary, you can get
micropore 1-gallon jugs from http://www.fungi.com and alot of
the gear you would need, obtaining a pure strain sounds
like the tricky part, culturing and selection of
pure-looking samples a couple times should do it. LSD
must be synthesized, it's such a beautiful molecule...

Piglet (posted 05-21-98)

Fan of Shulgin: I checked out the 'Operation Julie' book
and it says that the Ergot compounds were ALL bought.
Initially by simply driving to Switzerland and paying
cash (those were the days!) and later using fake
companies and from underground sources (Brotherhood of
Eternal Love with Leary et all).

I have never read of any large LSD manufacturers making
there own. It is quite a skill & is quite dangerous
(ergot IS classed as a poison, do you like your
extremeties? Do you want them to go black and drop off?
Don't try growing ergot without knowing the safety rules)

Someone I know was in prison with Kemp (the Julie
main-man) and Kemp is a 1 in a million brainiac.

The book 'Operation Julie' has a few pictures of the
chemistry setup. It was pretty involved stuff. One small
hilight was a brown bottle featured slap-bang in the
middle of one picture. It said 'NaNO2'. Fester says that
this 'might' be a replacement for acetyl-acetone. It is.
THAT was the Method-X bit. It's not even a secret.

drone 342 (posted 05-21-98)

Here's a thought:

What about using DCC as your dehydrating reagent for
forming an amide bond? High yields and low temps means
better product in larger quantities.

Much of the fancy-schmancy technology devoted to peptide
synthesis is equally applicable in this situation as
well. There's a ton of ways to go from an acid to an
amide, and its good to have as many as possible in one's
repetoire.

oh yeah, DCC is "DiCyclohexylCarbodiimide".

Structure:
(C6H12)-N=C=N-(C6H12)

The reaction converts this to dicyclohexylurea.

KrZ posted (05-22-98)

JLF sells pure claviceps purpea 1 gm for 10.00.

drone 342 (posted 05-22-98)

Re: Claviceps. That doesn't sound like too good of a deal. Do they have better prices when you buy in bulk?
Even at half the price, that really isn't too good a deal. Considering the tiny percentage of ergot alkaloids
in a gram, then considering how much less you have after hydrolyzing off those useless peptides, and how much less
you have still after the dehydration of the acid with ethylamine, ten dollars is way more than street prices.
This isn't even counting in labor as a cost (most chemists I know like to get paid.)

josh (posted 05-22-98)

Hey drone, would you post a synth. for lsd using bromocryptine.This synthesis that you have briefly
described is very interesting.This bee would greatly appreciate it.

Ritter (posted 05-22-98)

I'm no expert on Grignards, however do you really feel you could get the -Br to react w/ Mg to make the
Grignard? My experience has been that its pretty freakin' difficult to make tender complicated multi-cyclic
molecules such as bromocryptine undergo Grignard formation. I only skimmed your comments above and may be
reiterating what you stated but I think the best way to go about this would be to hydrolyze off the peptide
garbage leaving bromo lysergic acid and then subject this to Grignard's reaction. I think the appropriate time to
form the amide is after the Grignard because a carboxyl group will probably be less reactive than an amide group
towards the Grignard.

drone 342 (posted 05-24-98)

Ritter,

Yes, Grignard will work wonders in this case, and no, it
actually is easy to get it to do it. All that multicyclic
studd simply doesn't appeal to the grignard substituent
- it's looking for an electron-deficient site labile and
with nowhere to run to. Amides are surpisingly sturdy to
these condsitions, and will not readily react at all. As
far as I see it, that would really be the only concern
(regarding the carbonyls found therin.)The reason for
this is that the nitrogen is electron donating, whereas
in any other carbonyl, it doesn't have this luxury, and
will react readliy with a Grignard. Conditions are a
snap, just a nice dry ether soultion or Benzene solution
(with light being thoroughly eliminatined from the
envronment around the flask) of the free base of your
ergot caompound in question will do. If you're still
worried about that reaction affecting the peptide, just
save it for the last step - make bromo-LSD, then do it.
I guaruntee that the amide will be safe.

Quirks,

Thank you. This is the useful type of information we need buckets of if we want to end the war on drugs
(my strategy: an all-out assault; a psychedelic blitzkrieg. Hey, now that's a catchy phrase!)

drone 342 (posted 05-24-98)

Fan of Shulgin,

Where can you get a living 1-gram clean specimen of claviceps purpurea? Are you sure its alive? How do you
know this works, or is this strictly speculation?

Josh,

Tell you what; I'll give the ref's, and anybody with the resources to actually perform this should also
have plenty of access to the library. Actually, all you need is a copy of a decent lab manual describing the
synthesis of grignard reagents, and follow the general guidelines for producing a Grignard intermediate. Then,
add water. You now have ergocriptine. Hydrolyze it and condense with diethylamine according to the proceedures
listed in TiHKAL.

Alternatively, one could use DCC. From the Encyclopedia of Reagents for Organic Synthesis:

Typically, DCC (1.1 equiv) is added to a concentrated solution (0.1-1.0M) of the carboxylic acid (1.0 equiv),
amine (1.0 equiv), and catalyst (when used) in methylene chloride or acetonitrile at 0°C. The hydrated DCC
adduct, dicyclohexylurea (DCU), quickly precipitates and the reaction is generally complete within 1 h at rt..."

Downsides: THF and DMF screw things up by slowing things down and ecouraging the production of side-products, as
well as racemizing the carboxylic acid. The other downside is in some solvents, a trace of DCU can disolve
in with your product, requiring purification (nothing flash chromatography wouldn't take care of quite easily,
which you have to do anyways if you want to be a good person.)

Piglet (posted 05-26-98)

Fan Of Shulgin: When I typed about the dangers of ergot, I meant to to guy producing it. The actual amount of
ergot needed to produce 'St. Antonys Fire' immediately seem quite low. It was estimated from the last outbreaks
(after WW2 when people were starving and would eat ANYTHING including infested rye) that about 30mg causes
SEVERE reactions. I know you would never ingest such amounts of ANY substence in a lab, but growing your own
ergot is not a lab technique. I did check out that old chestnut about growing in culture. Most of the
researchers had little success. I think it CAN be produced in culture, but only by someone who REALLY knows
there stuff. Sandoz grow rye to this day!

drone 342 (posted 06-10-98)

Piglet, where did you get this information about Sandoz? As far as I know, Claviceps is one of those organisms
that researchers have spent a lot of time, money, and energy in getting it to grow in submerged culture on a
large scale -- and have come up with a successful means of doing so. I've heard some similar things in
publications from times past, but I suspect that in modern industry, the transition has been made.

Cherrie Baby (posted 06-11-98)

"Where can you get a living 1-gram clean specimen of claviceps purpurea?"

During late summer have a look at the Rye grass in the local park. You'll notice a purple-brown "ear" growing on
the rye seeds - this stuff is Claviceps purpurea. It grows in my back garden. If you have some experience with
shrooms this is easy to grow. The big catch is that nearly all the LSA producing ergot has been from particular strains
which you'll have to get from a lab that stocks pure cultures. I don't think wild ergot would work when making LSA's.
I've been told that you can grow the ergot (easily) but it won't make LSA unless it's the right strain!

Are there any biochemists out there who know the answer to this one way or another?

Forest Gump (Posted Dec. 24, 1997)

The book that you refer to "Practical LSD Manufacture" by Uncle Fester, now in
its 2nd Ed. isn't completely about LSD, although from the title one could get
that impression. The first edition contianed 115 pages, of which only about 70
pages actually had anything to do with LSD synthesis, the rest mostly about
Fester's pet project: TMA-2 synthesis. The second edition contains 142 pages,
almost all the extra pages going to his pet project -- which now consumes about
halve the book -- while the LSD portion remains virtually unchanged (all the
errors and mistakes of the first edition were remarkably well preserved into
the second). A naive person could be forgiven for mistakenly thinking the book
of being just a vehicle for his pet project -- but of course we know better.

Before I list just some of those errors let me preface it with this: it is
obvious that not only does Fester not have any practical experience with
Lysergic chemistry, but that he is also confused by it.

Isomer Confusion. In chapter 4 Fester makes repeated mistakes as to
chirality. On page 24, in reference to the anhydrous hydrazine degradation
method, he tells us that this procedure produces very little iso- compound,
when in fact it produces predominately iso- material. On page 25 he informs
us of the importance of maintaining anhydrous conditions to avoid getting
racemic product -- on further reading it is obvious that by "racemic" he
means iso/normal mixtures, as nowhere is there to be found any reference
to the l (levo) compound.

The older hydrazine hydrate method produced a 1/1 mixture of d and l compounds;
the l compounds are inactive and represent a total loss, as there is no
convenient method to convert them into the desired d compound. The anhydrous
hydrazine method is a newer improvement upon this which avoids the l compound,
but it still gives about 2/3 of the iso- compound which is also inactive; 2/3
inactive product sounds real bad, but it's not nearly as bad as the older
method because the iso- compound is easily isomerized into the active compound
in about 2/3 yield. When Hofmann refers to this new method as not producing any
"racemic" material what he means is that it doesn't produce any of the useless
l compound, not that it doesn't produce iso- compound.

Also, the amidation procedure he gives in the same chapter produces some iso-
compound, although nowhere does he mention that. Indeed, from reading the
purifacation procedure, he seems to think that this amidation method also
preserves chirality.

Continuum Error. The first paragraph on page 27 (i.e., "Both of these
choices are really very poor, ...") picks up from nowhere, and we're left to
wonder what he's refering to. Chalk this one up to bad proofreading (this is
Loompanics we're talking about after all).

Outdated Methods. The four amidation methods in the book have long since
been superseded by the phosphorus oxychloride in chloroform method, which is
not in the book.

Method X. In the book a big deal is made about his erroneous discovery of
a "superior" LSD method which he calls "method x". I'll spare you all the
convoluted details and inane logic of how he came about this "discovery" except
for this one statement of his: "Note that propionic anhydride is a listed
chemical under the Chemical Diversion Act, with a reporting threshold of 1 gram.
There is only one substance in the field of clandestine drug manufacture where
1 gram is a significant amount -- LSD"

I'm sure not a few DEA chemists must have laughed there ass off after having
read that. Propionic anhydride is used to make fentanyl and its analogues.
Some fentanyl analogues are 10 times more potent than LSD!!!!

And that is just some of the errors contained within that book. And with that
I'll leave you, hopefully a little bit more knowlegable.

FX (Posted Dec. 25, 1997):

Hey, thanks a lot. You seem to know quite a bit about LSD chemistry. I'm sure
that Fester's book has some errors, but I am not aware of any other book in
existence on practical LSD manufacture. Are you? It is amazing how few people
know anything about LSD synth, apparently it is the hardest recreational drug
to manufacture of them all, much much harder than ectacy or meth. Why is this?
How should someone go about learning about LSD manufacture assuming that they
don't have PhDs in chemistry? According to DEA, almost all of the LSD made in
the United States is made but just a handful of chemists in california! Can
you believe that? A half a dozen people make amost 100 million hits per year,
and they have been doing it since the 1960s! This almost blows the mind!

Forest Gump (Posted Dec. 25, 1997):

Below are all the books that are in print that I know of which contain LSD synthesis procedures:

So, which ones do I recomend for someone serious about LSD chemistry? Well,
all of them! But not for the reasons you might think at first.

Most of these books contain serious errors. The Anarchist Cookbook for example
has a method of "Making LSD in the kitchen" which is incorrect of course,
although it does give an accurate procedure which is merely a reprint of the
first part of Pioch's patent method. The Book of Acid calls to use sodium
nitrate in one method, when in fact it is sodium nitrite which is used in that
procedure. Recreational Drugs doesn't really contain anything that wasn't already
in Psychedelic Chemistry, although it does give an incorrect LSD structure. All
these books can go a long way in developing one's critical faculties though --
which is an important attribute for an LSD researcher to have, considering the
B.S. factor that surrounds LSD.

So, which of these books do I think are the most important to have?
All the books listed below, in order of importance:

Again, not for all the obvious reasons. Number 1 and 2 contain many journal
references, and so can be a good step-off point to the real gold mine: the
chemical journals at your nearest university science library. TIHKAL and #1
both have the most up-to-date method, although that's the only method TIHKAL has.

Believe it or not, you can probably start learning about LSD chemistry right
now if you have a chemistry text-book or are near any library. Just look-up the
following (numbered in order of importance):

carboxyl group;

carboxylic acids;

amides;

amines;

also, look-up:

acid halides;

anhydrides;

mixed anhydrides;

hydrazides;

azides;

azoles;

esters;

and of course, alkaloids.

You see, LSD is an amide. LSD is usually made from lysergic acid which is a
carboxylic acid and diethylamine which is an amine. Lysergic acid is in turn
usually made by degradation of an amide, such as ergotamine.

All of these procedures involve the changing of one functional group: the
carboxyl group. A good LSD chemistry researcher will devote much (MUCH) study
to this group.

I hope that this has been helpful.

Forest Gump:

CB: (2) Another dodgy thing about Fester's "Practical LSD Manufacture" is his
recommendation to make LSAs by growing ergot on rye and to plant your own rye
field in order to do this! Is the man mad? Fester appears to be ignorant of the
existence of C. paspali.

FG: Yes, Fester is a bit loopy to think that prospective LSD chemists are going
to become Farmer for a Year. Although the method certaintly works, the labor and
amount of solvents required make it impractical for one or two people.

Some more references:

CB: (4) In D. M. Perrine's book "The chemistry of mind-altering drugs" pages
274-278 outline syntheses of LSD. He includes both modern total synthetic
methods and clandestine methods [he figures that lysergic acid is made from
either growing C. paspali to produce paspalic acid OR by diverting LSA from
medicines]

CB: (5) In M. V. Smith's"Psychedelic Chemistry" growth of C purpurea on
synthetic media is described. Just about everyone claims that C purpurea will
only grow on grain in a field. What's Up Doc?

FG: Getting species of Claviceps to grow in culture is easy. Getting species
of Claviceps to grow in culture and produce lysergamides' is what's hard.
I'm sure M. V. Smith's method in said book will work just fine for growingClaviceps species, but it will all be for nought, as no lysergamides' will
be produced by it.

Successful culture methods have been developed which use specific strains of
both C. paspali and C. purpurea to produce as much as 2 to 5 g of lysergamides
per liter of culture!!!!

I direct you to "Biosynthesis of Ergot Alkaloids and Related Compounds",
Tetrahedron, Vol. 32, pp. 873-912 (1976). On page 883 under the heading
"Industrial production of ergolines" it gives a brief overview of what I
just mentioned, and gives references to those procedures.

Life History and Poisonous Properties of Claviceps paspali;
H. B. Brown (Mississippi Agricultural Experiment Station);
Journal of Agricultural Research, Vol. 7, No. 9, pp 401-405.
Describes on brief glance through it - germination of the yellowish-grey sclerotia found on Paspalum dilatatum Poir. observed in the region of the Mississippi Agricultural College. Also contains reference to Stevens and Halls' original article (1910).

Biotechnological Exploitation of the Ergot Fungus (Claviceps Purpurea);
Karl Esser and Andrea Duvell; Process Biochemistry, August 1984 pgs 142-149.Synopsis: "The alkaloids of the ergot fungus C. purpurea and related species
already known as drugs in the middle ages are still finding many uses in
medical therapy (he he). Since the supply of natural grown ergots is not
sufficient, the biotechnological production of ergot alkaloids has gained in
importance. This requires not only an undestanding of physiological and
environmental conditions, but also concerted breeding in order to increase
and stabilize the production level".

Biology of Claviceps; Willard A. Taber; Chapter 15 (sorry - i don't remember
which book this came from, but it should be indexed under Taber in Biological
Abstracts) pgs 449-486.
"If one desires isolates of C. paspali (which are high producers of simple
amides), one must go to paspalum grass. ... C. paspali differs from all other
species in possesing a yellowish tan cauliflower- shaped sclerotium rather
than the purplish banana-shaped sclerotium, and it has been suggested that
this species be trasnsferred to the genus Mothesia."

The Ergot Alkaloids; A. Stoll and A. Hofmann (THE);
Chapter 21, The Alkaloids, Manske (ed. ?) vol. VIII, pgs 725-779+.
Describes lots and lots and lots of chemical detail regarding everything from
biogenesis to complete chemical synthesis as a means of confirming structure.
Also has a section completely devoted to "Derivatives of Ergot Alkaloids" in
which the following processes for synthesizing amides are discussed:

The azide process.

DMF-SO3 mixed anhydride method.

mixed Lysergic acid trifluoroacetic anhydride.

Lysergic acid chloride hydrochloride method.

N,N'-carbonyldiimidazole as condensing agent (Best IMHO).

Kobel, Schreier, Rutschmann.Helv. Chim. Acta, 47, 1052 (1964)

Subject: LSD in the Literature

Certainly making LSD from 'scratch' is not currently thought to be cost effective, however, a variety of publications exist describing how. I realize that this compilation may be above most of your heads however some of the more serious of you might be interested in some of the literature describing various LSD syntheses. If you know of others please post them.

A short synthesis of the 8-azaergoline ring system by intramolecular tandem decarboxylation-cyclization of the Minisci-type reactionDoll MKH
J Org Chem 64, 1372-1374 (1999)

New synthesis and characterization of (+)-lysergic acid diethylamide (LSD) derivatives and the development of a microparticle-based immunoassay for the detection of LSD and its metabolites
Li Zy, Gocszkutnicka K, McNally AJ, et al.
Bioconjugate Chem 8(6) 896-905 (1997)

Synthesis of LSD-25

Originally published in 1967 as "The Psychedelic Guide to Preparation Eucharist" by Robert E. Brown.

Preparatory arrangements

Starting material may be any lysergic acid derivative,from Claviceps purpures(ergot) on rye grain or from culture, from
Ipomea (morning glory) seeds, or from synthetic sources. Preparation #1 uses any amide, or lysergic acid as
starting material. Preparations #2 and #3 must start with lysergic acid only, prepared from the amides as follows:

10 g of any lysergic acid amide from various natural sources is dissolved in 200ml of mathanoic KOH solution and the
methanol removed immediately in vacuum. The residue is treated with 200ml of an 8% aqueous solution of KOH and the mixture
heated on a steam bath for one hour. A stream of N2 gas is passed through the flask during heating and the evolved NH3 in
the gas stream may be titrated in HCL to follow the reaction. The alkaline solution is made neutral to congo red with tartaric
acid,filtered,cleaned by extracting with ether, the aqueous solution filtered and evaporated. Digest with MeOH to remove
some of the colored material from the crystals of lysergic acid.

Arrange the lighting in the laboratory similarly to that of a darkroom. Use photographic red and yellow safety lights since
lysergic acid derivatives are decomposed by light. A weak, long wave ultraviolet source is conveniently made from the purple
glass filter used in the 1950 ford dash lighting system. A small tungsten bulb will provide enough light.

Have plenty of aluminum foil handy to cover reagents and products when light is present. Rubber gloves must be worn due
to the highly poisonous nature of ergot alkaloids. A hair dryer, or, much better, a flash evaporator, is necessary to speed up
steps where evaporation is necessary.

Preparation #1

Step I - Use Yellow Light

Place one volume of powdered ergot alkaloid material in a tiny roundbottom flask and add two volumes of anhydrous
hydrazine. An alternate procedure uses a sealed tube in which the reagents are heated at 112°C. The mixture is
refluxed (or heated) for 30 minutes. With an open condenser, keep an inert atmosphere on the reaction. Add 1.5 volumes H2O
and boil 15 minutes. On cooling in the refrigerator, isolysergic acid hydrazide is crystallized.

Step II - Use Red Light

Chill all reagents and have ice handy. Dissolve 2.82 g of the hydrazide rapidly in 100ml 0.1 N ice-cold HCl using an ice
bath to keep the reaction vessel at 0°C. 100ml ice-cold 0.1 N NaNO2 is added and after 2 to 3 minutes vigorous stirring,
130ml more HCl is added dropwise with vigorous stirring again in an ice bath. After 5 minutes, neutralize the solution with
NaHCO3 saturated sol. and extract with ether. Remove the aqueous solution and try to dissolve the gummy substance in ether.
Adjust the ether solution by adding 3 g diethylamine per 39ml ether extract. Allow to stand in dark, gradually warming up to
20°C over a period of 24 hours. Evaporate in vacuum and treat as indicated in the purification section for conversion of
iso-lysergic amides to lysergic acid amides.

Preparation # 2

Step I - Use Yellow Light

5.36 g of d-lysergic acid are suspended in 125ml of actonitrile and the suspension cooled to about -20°C
in a bath of acetone cooled with dry ice. To the suspension is added a cold -20°C solution of 8.82 g of trifluoroacetic
anhydride in 75ml of acetonitrile. The mixture is allowed to stand at -20°C for about 1.5 hours during which time
the suspended material dissolves, and the d-lysergic acid is converted to the mixture anhydride of lysergic and
trifluoroacetic acids. The mixed anhydride can be separated in the form of an oil by evaporating the solvent in vacuum at a
temperature below about 0°C. Everything must be kept anhydrous.

Step II - Use Red Light

The solution of mixed anhydrides in acetonitrile from Step I is added to 150ml of acetonitrile containing 7.6 g of
diethylamine. The mixture is held in the dark at room temperature for about 2 hours. The acetonitrile is evaporated in
vacuum, leaving a residue of LSD-25 plus other impurities. The residue is dissolved in 150ml of chloroform and 20ml of ice
water. The chloroform layer is removed and the aqueous layer is extracted with several portions of chloroform. The chloroform
portions are combined and in turn,washed with four 50ml portions of ice-water. The chloroform solution is then dried over
anhydrous Na2SO4 and evaporated in vacuum.

Preparation # 3

The following procedure gives good yield and is very fast with little iso-lysergic acid being produced, however, the stoichometry must be exact or yields will drop.

Step I - Use White Light

Sulfur trioxide is produced in an anhydrous state by carefully decomposing anhydrous ferric sulfate at approximately 480°C. Store under anhydrous conditions.

Step II - Use White Light

A carefully dried 22 liter RB flask fitted with an ice bath, condenser, dropping funnel and mechanical stirrer is
charged with 10 to 11 liters of dimethyformamide (freshly distilled under reduced pressure). The condenser and dropping
funnel are both protected against atmospheric moisture. 2 lb. of sulfur trioxide (Sulfan B) are introduced dropwise, very
cautiously with stirring, during 4 to 5 hours. The temperature is kept at 0-5 degrees throughout the addition. After the
addition is complete, the mixture is stirred for 1-2 hours until some separated,crystalline sulfur trioxide-dimethylformamide
complex has dissolved. The reagent is transferred to an air-tight automatic pipette for convenient dispensing, and kept
in the cold. Although the reagent, which is colorless may change to yellow and red, its efficiency remains unimpaired for three
to four months in cold storage. An aliguot is dissolved in water and titrated with standard NaOH to a phenolphthalein end point.

Step III - Use Red Light

A solution of 7.15 g of d-lysergic acid monohydrate (25 mmol) and 1.06 g of lithium hydroxide hydrate (25 mmol) in 200 L
of MeOH is prepared. The solution is distilled on the steam bath under reduced pressure. The residue of glass-like lithium
lysergate is dissolved in 400ml of anhydrous dimethyl formamide. From this solution about 200ml of the dimethyl formamide is
distilled off at 15mm pressure through a 12- inch helices packed column. The resulting anhydrous solution of lithium lysergate
left behind is cooled to 0 degrees and, with stirring, treated rapidly with 500ml of SO3-DMF solution (1.00 M soln). The mixture
is stirred in the cold for 10 minutes and then 9.14 g (125.0 mmol) of diethylamine is added. The stirring and cooling are
continued for 10 minutes longer, when 400ml of water is added to decompose the reaction complex. After mixing thoroughly, 200ml
of saturated aqueous NaCl solution is added. The amide product is isolated by repeated extraction with 500ml portions of
ethylene dicloride. The combined extract is dried and then concentrated to a syrup under reduced pressure. Do not heat the
syrup during concentration. The LSD may crystallize out, but the crystals and the mother liquor may be chromatographed according
to the instructions on purification.

Purification of LSD-25

The material obtained by any of these three preparations may contain both lysergic acid and iso-lysergic acid amides.
Preparation #1 contains mostly iso-lysergic diethylamide and must be converted prior to separation. For this material, go to Step II first.

Step I - Use Darkroom and follow with Long Wave UV

The material is dissolved in a three to one mixture of benzene in chloroform. Pack a chromatography column with a
slurry of basic alumina in benzene so that a one-inch column is six inches long. Drain the solvent to the top of the alumina
column and carefully add an aliquot of the LSD-solvent solution containing 50ml of solvent and 1 g LSD. Run this solution
through the column, following the fastest moving blue fluorescent band. After it has been collected, strip the
remaining material from the column by washing with MeOH. Use the UV light sparingly during this procedure to prevent excessive
damage to the compounds. Evaporate the second fraction in vacuum and set aside for Step II. The fraction containing the pure LSD
is concentrated in vacuum and the syrup will crystallize slowly. This material may be converted to the tartaric acid and the LSD
tartrate conveniently crystallized, mp 190-196°C

Step II - Use Red Light

Dissolve the residue derived from the methanol stripping of the column in a minimum amount of alcohol. Add twice that volume
of 4 N alcoholic KOH solution and allow the mixture to stand at room temperature for several hours. Neutralize with dilute HCl,
make slightly basic with NH4OH and extract with chloroform or ethylene dicloride as in preparations #1
or #2. Evaporate in vacuum and chromatograph as in the previous step.

Salvage

Neutralize all leftover solutions and residues with NaHCO3 and evaporate in vacuum to low volume. Extract with ammoniacal
chloroform and evaporate the extract to dryness. This residue may be run through the whole process again and more LSD will be produced.

Storage and use

Lysergic acid compounds (among them LSD) are unstable to heat, light and oxygen. In any form it helps to add ascorbic
acid as an anti-oxidant, keeping the container tightly closed, light-tight with aluminum foil, and in refrigerator.

Packaging for use presents many possibilities, partially due to the incredibly small dosage involved. First a bio-assay
of the solvent is made, then it may be measured by the volume of the solvent it is in. The solvent may be evaporated onto a
weighed, calculated amount of some inactive powder such as chalk. sugar or baking soda. This bulky powder may be easily
encapsulated in weightable portions. It is advantageous to add a trace of dry ascorbic acid to the dried powders. Sugar cubes
offer a handy but extremely notorious method of dispensing. Other methods are without number, here being offered just a few
occasionally used by the criminal element. Gelatin capsules are coated with the liquid solution and the capsules filled with an
inert substance. Decoys such as this inert mixture might include a trace of brown color, a trace of quinine for fluorescence, and
a trace of some relatively non-toxic compound which nearly mimicas the infra-red spectrum of LSD. For transport, a smuggler
might evaporate a considerable amount onto a pocket handkerchief or onto a sheet of paper, providing the solution was properly
decolorized before such treatment. These underhanded methods are used by criminals to avoid punitive action by law enforcement enthusiasts.

One gram of pure LSD, if used in a truly enlightened, careful manner can be the door to a magnificent experience to nearly 3,000 individuals.
Used furtively and in ignorance, the same amount may bring terrible confusion and abject terror to nearly one-third of these.

Note:JMC 35(2), 203-211 (1992) has some amazing stereoviews of LSD which might interest non-chemists who like to cross their eyes...

From:chrle@mursuky.campus.mci.net

As a public service to alt.drugs I have posted the following with some comments by myself. The following is a good example of the credo:
A handful of refs does not a chemist make. I found this on one of the drug info sites. I've number the lines for commenting.

LSD Synthesis

of d-lysergic acid monohydrate and 4.45g (99 mmol) of diethylamine was

brought to reflux by heating. Heat was removed, and reflux was maintained

by the addition of 2 mL (3.4g, 22mmol) of phosphorous oxychloride (POCl3)

over a 2 minute period. The mixture was then refluxed for an additional

4-5 mins until an amber-colored solution resulted. The solution was

brought to room temperature and was washed with 200ml of 1M NH4OH.

The CHCl3 solution was dried (MgSO4), filtered, and concentrated under vacuum

(not allowing the solution to exceed 40°C). The last traces of the solvent were removed at 2-5 mmHg. The viscious residue
was dissolved in a minimum amount of MeOH and acidified with a freshly prepared 20% solution of maleic acid in MeOH. Crystallization occured
spontaneously. The needles were filtered, washed with cold MeOH and air-dried. Yield was 66% after further purification by column
chromatography over alumina (Brockman) and elution with 3:1 benzene-chloroform. The chromatography takes appx 8-9
hours. Alternatively, it can be crystallized as the (+)-tartrate from MeOH. After crystallizing from cold MeOH, it is diluted with ethyl
acetate, filtered and the the crystals are washed with ethyl acetate.

This procedure also works for primary amines and small dialkyl amines. LSD, however, probably remains the most worthwhile product. Other
interesting amines might be the N-ethyl-N-propyl derivative (LEP) and the morpholide (LSM-775). 75µg of the morpholide have been reported
to have been as effective as 50µg of d-LSD but with 45 min onset (vs 1 hour) and a 1 hour peak (vs 4 hours). The procedure would probably
work well for LEP, but yields would be reduced for the morpholide. Other N20-alkyl-lysergic acid derivatives tend to be more than 10
times less potent than LSD if not effectively inactive. N6-ethyl- (and allyl/propyl) derivates of LSD may be more active than
LSD itself, but synthetic routes to these chemicals presently start with LSD and yields would probably inhibit their appearance on the
illicit market. (N6 is the other nitrogen on the ring structure in addition to the N1 pyrrole/indole nitrogen). Derivatives
of LSD (besides LSA/LA-111 and lysergic acid) are not scheduled, but would be prosecutable under the designer drugs act after testimony
from a DEA agent that in their opinion the defendant was planning to distribute them.

Line 2: The 3.25g of d-lysergic acid monohydrate is suppose to be
dissolved in 150ml of CHCl3. 96mmol of diethylamine is supposed to be
used and 96mmol of this is ~7.1g, not 4.45g...(where's a good periodic
chart when you need one?). The 7.1g of diethylamine is supposed to be
dissolved in 25ml of CHCl3.

Line 3-4: To the 3.25g of d-lysergic acid monohydrate dissolved in
150ml of CHCl3 that is undergoing reflux is added the
diethylamine/CHCl3 solution and 2 ml of POCl3. These
are added simultaneously from separate dropping funnels over 2-3
minutes. Method B

Line 8: The CHCl3 is dried... What? Yes, it's dried but this is the first time that the
procedure that was given in this "how to" even makes mention of it! Of course, all of this is made very clear in the ref:
[Johnson, Ary, Teiger, Kassel. "Emetic Activity of Reduced Lysergamides."
Journal of Medicinal Chemistry 16(5), 532-537 (1973)]

It's pretty clear that this "how to" was posted by someone with little or no chemical expertise who had a couple of refs in hand, ran to the
local college library, photocopied the papers, typed up this mess and posted it for the benefit (ha!) of others.

So, do you still want to attempt a synthesis of LSD? Yes? Well get the refs and get the whole story. A few chemistry classes wouldn't hurt either.

When I saw the subjects relating to the synthesis of LSD, I knew the information would be outdated. It's humourous to see people who think
they're in the know giving out info that was outdated even in the 70's.

Lysergic acid amides are commonly made by a simple and efficient procedure using POCl3 and the desired amine in CHCl3 solution. I doubt that this
procedure is used by the majority of clandestine chemists, but since I don't know any, I wouldn't know. By the description of the procedure,
it's simple and uses relatively safe reagents (I have a reference, but not handy...) And you won't find it in any obvious places even in the
most recent Merck because LSD is not the product of focus in the article.

This is why I doubt that unsavvy clandestine chemists would be using this procedure. But according to the article, the method has a broad scope
and has been used by Nichols and Oberlender for some other lysergic acid amides. (The article in question regards 9,10-saturated derivatives
tested for emetic properties). It's time to stop turning to those stupid "how to make your very own drug" guides and learn how to read real chemsitry
literature. If you can't, don't bother...

Even the synthesis of lysergic acid is outdated. Rebek has described an extremely elegant synthesis of methyl lysergate from L-tryptophan
which gives only the natural isomer of lysergic acid. It's still a several step procedure, but most of the reagents are fairly common and the
yields are greatly improved over past syntheses.

This brings me to an interesting side-note. Several years ago, analogues of LSD that were 2 and 3 times as potent as LSD were synthesized. These
went largely unnoticed and would most likely prove of little interest to clandestine chemists because LSD was the precursor used and the loss
in synthesis outweighed the gain in potency. But using Rebek's synthesis, one could simply alter the procedure slightly and intorduce the groups
that make the compounds more potent. When the 6N-methyl group is replaced by ethyl or allyl, it becomes 2 and 3 times as potent respectively.

I am posting this for general information. I may post references if I decide it would be prudent. Requests will be ignored and I ask you not to
send e-mail requesting references. But if you just want to chat about them and maybe speculate on subjective effects or other avenues of substitution...
I don't know if I'll ever see the day that research in this area is open and legal, but I'd love to...

I still feel like making a disclaimer that I am not encouraging this information to be used to synthesize illegal compounds, but for
personal enlightenment. It's time to pull chem-wannabe's out of the Dark Ages!